The present invention relates to a device for receiving liquids and also to a device for applying liquids on sample carriers and to a corresponding method for this purpose.
The trend in biotechnology leads to the processing of increasingly smaller quantities of liquid. The reasons for this are very varied. Often the substances to be examined are very expensive since usually in fact a large number of steps is required for the production thereof. In part they concern biologically dangerous materials, the handling of which in very small quantities can reduce the risk enormously. However frequently also only very small quantities of the sample volume are available but, at the same time, as many tests as possible are intended to be implemented. Also the speed of the reactions depends significantly upon the sample volume. The smaller this is, the faster the analysis. Modern diagnosis apparatus is able to analyse thousands of adjacently printed spots at the same time on one microarray.
Over the years, specific standards in tests have been established. Thus frequently disposable articles made of injection-moulded polypropylene or polystyrene are used since the very costly cleaning and disinfection of the sample containers is thus dispensed with. These microtitre plates can be found in various designs. They differ mainly in the number of sample volumes. Thus there are 96-, 384- but also 1536-well plates which in fact have the same outer dimensions but differ in the volume and number of wells.
The difficulty resides in placing the reagents from the wells on the microarray. Simple metering methods with pipettes and by hand are very time-consuming and imprecise. In order to avoid cross-contaminations, the pipette tip must be exchanged after each sampling. This is also the reason why piezo dispensers which firstly remove the liquid and then place it on the microarray are not possible.
Previous approaches to the solution are restricted either to a completely new configuration of the sample container (MTP) or the volume is placed on the sample carrier via an intermediate station, i.e. not directly.
In the case of the “TopSpot-Method”, a print head made of silicon and glass is manufactured and a series of microchannels conducts the liquids then into the specially produced nozzles. A pressure pulse is produced via a plunger and places the drop at the outlet of the nozzle. The disadvantage of this method resides in the fact that, for each new printing process, the print head must firstly be disinfected and cleaned in order to preclude cross-contamination. In addition, the production of these print heads is relatively complex and expensive. A further disadvantage of the method resides in the fact that the printed grid always has a fixed spot spacing of for example 500 μm. The wells can only all be printed at the same time and in a fixed position. Before printing can take place with this method, the print head must firstly be filled since printing cannot take place directly from the reaction vessel. The dead volume is high due to the long channels.
The “Dispensing Wellplate (DWP) method” functions similarly. The metering volume here is however not controlled via the pulse duration or the stroke but the entire micronozzle which has a strictly defined volume is emptied.
A third variant is the removal of the desired quantity of liquid via “pipettes” which then “deposit” this on the sample carrier. The great disadvantage in this variant is contamination of the pipette. After each printing process, said pipette must be cleaned, which results inter alia in the fact that a part of the liquid is always lost. The danger of cross-contaminations with this method is very high.